+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-19040 | ||||||||||||
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タイトル | Structure of Integrator-PP2A-SOSS-CTD post-termination complex | ||||||||||||
マップデータ | Overall map filtered by local resolution | ||||||||||||
試料 |
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キーワード | Integrator complex / Post-termination complex / RNA Polymerase II / Pol II / RNAPII / TRANSCRIPTION | ||||||||||||
機能・相同性 | 機能・相同性情報 SOSS complex / U2 snRNA 3'-end processing / regulation of fertilization / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / regulation of microtubule binding / snRNA 3'-end processing / MASTL Facilitates Mitotic Progression / regulation of meiotic cell cycle process involved in oocyte maturation ...SOSS complex / U2 snRNA 3'-end processing / regulation of fertilization / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / regulation of microtubule binding / snRNA 3'-end processing / MASTL Facilitates Mitotic Progression / regulation of meiotic cell cycle process involved in oocyte maturation / mitotic sister chromatid separation / protein serine/threonine phosphatase complex / protein phosphatase type 2A complex / meiotic sister chromatid cohesion, centromeric / establishment of protein localization to telomere / snRNA processing / peptidyl-serine dephosphorylation / peptidyl-threonine dephosphorylation / flagellated sperm motility / FAR/SIN/STRIPAK complex / protein localization to nuclear envelope / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / positive regulation of microtubule binding / Inhibition of replication initiation of damaged DNA by RB1/E2F1 / female meiotic nuclear division / protein phosphatase regulator activity / protein antigen binding / GABA receptor binding / integrator complex / regulation of transcription elongation by RNA polymerase II / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / Formation of RNA Pol II elongation complex / Formation of the Early Elongation Complex / Transcriptional regulation by small RNAs / RNA Polymerase II Pre-transcription Events / TP53 Regulates Transcription of DNA Repair Genes / FGFR2 alternative splicing / RNA polymerase II transcribes snRNA genes / mRNA Capping / mRNA Splicing - Minor Pathway / Processing of Capped Intron-Containing Pre-mRNA / RNA Polymerase II Promoter Escape / RNA Polymerase II Transcription Pre-Initiation And Promoter Opening / RNA Polymerase II Transcription Initiation / RNA Polymerase II Transcription Elongation / RNA Polymerase II Transcription Initiation And Promoter Clearance / RNA Pol II CTD phosphorylation and interaction with CE / Estrogen-dependent gene expression / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / mRNA Splicing - Major Pathway / Initiation of Nuclear Envelope (NE) Reformation / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / ERKs are inactivated / G-rich strand telomeric DNA binding / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / mitotic G2/M transition checkpoint / 加水分解酵素; エステル加水分解酵素; 3'-リン酸モノエステル産生エンドリボヌクレアーゼ / regulation of growth / Disassembly of the destruction complex and recruitment of AXIN to the membrane / inner cell mass cell proliferation / negative regulation of epithelial to mesenchymal transition / centrosome localization / negative regulation of glycolytic process through fructose-6-phosphate / positive regulation of NLRP3 inflammasome complex assembly / response to ionizing radiation / Platelet sensitization by LDL / CTLA4 inhibitory signaling / protein serine/threonine phosphatase activity / myosin phosphatase activity / protein-serine/threonine phosphatase / regulation of cell differentiation / T cell homeostasis / ERK/MAPK targets / mesoderm development / regulation of G1/S transition of mitotic cell cycle / positive regulation of telomere capping / phosphoprotein phosphatase activity / RNA polymerase II transcribes snRNA genes / DARPP-32 events / chromosome, centromeric region / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / lateral plasma membrane / negative regulation of hippo signaling / RNA polymerase II, core complex / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / DNA polymerase binding / Cyclin A/B1/B2 associated events during G2/M transition / core promoter sequence-specific DNA binding / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) / Sus scrofa (ブタ) / Trichoplusia ni (イラクサキンウワバ) | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.7 Å | ||||||||||||
データ登録者 | Fianu I / Ochmann M / Walshe JL / Cramer P | ||||||||||||
資金援助 | ドイツ, European Union, 3件
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引用 | ジャーナル: Nature / 年: 2024 タイトル: Structural basis of Integrator-dependent RNA polymerase II termination. 著者: Isaac Fianu / Moritz Ochmann / James L Walshe / Olexandr Dybkov / Joseph Neos Cruz / Henning Urlaub / Patrick Cramer / 要旨: The Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex ...The Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex consisting of Pol II, the DRB sensitivity-inducing factor (DSIF) and the negative elongation factor (NELF) and how it cleaves the nascent RNA transcript, but has not explained how Integrator removes Pol II from the DNA template. Here we present three cryo-electron microscopy structures of the complete Integrator-PP2A complex in different functional states. The structure of the pre-termination complex reveals a previously unresolved, scorpion-tail-shaped INTS10-INTS13-INTS14-INTS15 module that may use its 'sting' to open the DSIF DNA clamp and facilitate termination. The structure of the post-termination complex shows that the previously unresolved subunit INTS3 and associated sensor of single-stranded DNA complex (SOSS) factors prevent Pol II rebinding to Integrator after termination. The structure of the free Integrator-PP2A complex in an inactive closed conformation reveals that INTS6 blocks the PP2A phosphatase active site. These results lead to a model for how Integrator terminates Pol II transcription in three steps that involve major rearrangements. | ||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_19040.map.gz | 245.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-19040-v30.xml emd-19040.xml | 65.9 KB 65.9 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_19040_fsc.xml | 17 KB | 表示 | FSCデータファイル |
画像 | emd_19040.png | 45.5 KB | ||
Filedesc metadata | emd-19040.cif.gz | 16.4 KB | ||
その他 | emd_19040_additional_1.map.gz emd_19040_additional_2.map.gz emd_19040_additional_3.map.gz emd_19040_additional_4.map.gz emd_19040_additional_5.map.gz emd_19040_additional_6.map.gz emd_19040_half_map_1.map.gz emd_19040_half_map_2.map.gz | 56.1 MB 55.7 MB 96.2 MB 56 MB 55 MB 55.9 MB 340.5 MB 340.5 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-19040 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-19040 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_19040_validation.pdf.gz | 835.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_19040_full_validation.pdf.gz | 835.1 KB | 表示 | |
XML形式データ | emd_19040_validation.xml.gz | 23.7 KB | 表示 | |
CIF形式データ | emd_19040_validation.cif.gz | 31.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-19040 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-19040 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_19040.map.gz / 形式: CCP4 / 大きさ: 421.9 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | Overall map filtered by local resolution | ||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-追加マップ: Focused refined map around Integrator cleavage module (INTS4,...
ファイル | emd_19040_additional_1.map | ||||||||||||
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注釈 | Focused refined map around Integrator cleavage module (INTS4, INTS9 and INTS11) | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Focused refined map around INTS1, INTS2 INTS7 and DSS1
ファイル | emd_19040_additional_2.map | ||||||||||||
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注釈 | Focused refined map around INTS1, INTS2 INTS7 and DSS1 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Focused refined map around INTS5, INTS8 and INTS15
ファイル | emd_19040_additional_3.map | ||||||||||||
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注釈 | Focused refined map around INTS5, INTS8 and INTS15 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Focused refined map around INTS6 and PP2A
ファイル | emd_19040_additional_4.map | ||||||||||||
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注釈 | Focused refined map around INTS6 and PP2A | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Focused refined map around INTS3 and SOSS factors
ファイル | emd_19040_additional_5.map | ||||||||||||
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注釈 | Focused refined map around INTS3 and SOSS factors | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Focused refined map around INTS1 c-terminus and center of Integrator
ファイル | emd_19040_additional_6.map | ||||||||||||
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注釈 | Focused refined map around INTS1 c-terminus and center of Integrator | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_19040_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_19040_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : Post-termination complex
+超分子 #1: Post-termination complex
+超分子 #2: Integrator-PP2A complex and NABP2 and INIP
+超分子 #3: RNA Polymerase II C-terminal domain peptides
+超分子 #4: DSS1
+分子 #1: UNK-UNK-UNK-UNK-UNK-UNK-UNK-UNK-UNK
+分子 #2: SOSS complex subunit B1
+分子 #3: SOSS complex subunit C
+分子 #4: DNA-directed RNA polymerase subunit
+分子 #5: Integrator complex subunit 1
+分子 #6: Integrator complex subunit 2
+分子 #7: Integrator complex subunit 3
+分子 #8: Integrator complex subunit 4
+分子 #9: Integrator complex subunit 5
+分子 #10: Integrator complex subunit 6
+分子 #11: Integrator complex subunit 7
+分子 #12: Integrator complex subunit 8
+分子 #13: Integrator complex subunit 9
+分子 #14: Integrator complex subunit 10
+分子 #15: Integrator complex subunit 11
+分子 #16: Integrator complex subunit 14
+分子 #17: Integrator complex subunit 15
+分子 #18: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit...
+分子 #19: Serine/threonine-protein phosphatase 2A catalytic subunit alpha i...
+分子 #20: DSS1
+分子 #21: Integrator complex subunit 13
+分子 #22: ZINC ION
+分子 #23: MANGANESE (II) ION
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 0.3 mg/mL |
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緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 39.93 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: OTHER / 撮影モード: OTHER / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
+画像解析
-原子モデル構築 1
初期モデル | PDB ID: Chain - Source name: PDB / Chain - Initial model type: experimental model |
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得られたモデル | PDB-8rbz: |